Strategically Staged Tumor Ablation and Inflammation Suppression Using Shell‐Core Nanoparticles to Eradicate Bladder Tumors and Prevent Recurrence

Abstract Nanomedicine shows promise in the therapy of eradicating bladder tumors and preventing tumor recurrence caused by cancer‐related inflammation. Shell‐core structured BNN6/Z8@ALA/Z67 nanoparticles with sequential release kinetics is designed, aiming to eliminate tumors and curb inflammation, thereby ablating bladder tumors and preventing their recurrence. The shell of this nanoparticle comprises zeolitic imidazolate framework‐67 (Z67) and 5­aminolevulinic acid (ALA), while the core comprises zeolitic imidazolate framework‐8 (Z8) and N,N’‐di‐sec‐butyl‐N,N’‐dinitroso‐1,4‐phenylenediamine (BNN6). Modified with polydopamine‐methoxypolyethylene glycol amine, these nanoparticles efficiently target bladder tumors. In the acidic tumor environment, the outer‐layered Z67 breaks down rapidly, releasing ALA, which transforms into protoporphyrin IX (PpIX) in mitochondria. Additionally, the degraded Z67 triggers the conversion of hydrogen peroxide into oxygen, aiding PpIX to generate reactive oxygen species under ultrasound, facilitating tumor ablation. As Z67 decomposes, the inner‐layered Z8 releases BNN6 in the acidic environment. Ultrasound exposure prompts the release of nitric oxide, effectively reducing inflammation. Under ultrasound, BNN6/Z8@ALA/Z67 showcased outstanding staged anti‐tumor and anti‐inflammatory effects in both in vitro and murine subcutaneous tumor model tests, and effectively prevents tumor recurrence in rat bladder tumor models. These findings underscore the promising potential of the designed shell‐core nanoparticle with staged tumor ablation and inflammation suppression in preventing bladder tumor recurrence.